Carbon monoxide is a very versatile and common reagent in organic synthesis. Apart from its common use as reducing agent, several metal-catalysed carbonylative applications have been developed during the last 50 years.
In these reactions, gaseous CO is frequently used as the CO source. A catalyst “shuttles” CO from the gas phase to the substrate where a CO molecule is inserted to said substrate. The catalyst must have certain properties in order to shuttle CO(g). The catalyst should have a spontaneous affinity for CO; otherwise it will not bond to it.
The gaseous carbon monoxide source is conventionally used in reactions such as (a) palladium-catalysed carbonylations of aryl halides to an carboxylic acid or ester with water or an alcohol or to an amide with an amine; (b) metal-catalysed three component cross-coupling reactions between an arylmetal reagent, carbon monoxide gas and an aryl halide, often at high pressures to avoid side products (e.g. direct coupling); and (c) metal catalysed hydroformylation reactions. Still other methodologies (for example Ishiyama et al, Tetrahedron Letters, 1993, 34, 7595) resolve cross-reactivity problems by derivatizing the nucleophile or electrophile.
In one conventional method of performing carbonylation reactions, one starts with a metal carbonyl as a pre-catalyst (which by its very existence affirms the affinity of the metal for CO). In broad terms, the following sequence unfolds: irradiation by UV-light or thermal heating makes one CO dissociate from the metal carbonyl pre-catalyst liberating a free site on the metal; the substrate inserts itself to said free-site; a CO molecule originally bonded to the metal inserts to the substrate; the (carbonylated) product is eliminated generating two free sites; these sites are refilled with one new substrate molecule and CO from the gas phase; the cycle repeats itself until the CO or the substrate is fully consumed, or the catalyst is inactivated by, for example, poisoning. A schematic mechanism for these reactions is illustrated in FIG. 1.
In 1969, Corey (Corey E. J., Hegedus, L. S., Journal of the American Chemical Society, 1969, 91(5), 1233-1234) published early seminar work on the carboxylation of certain activated substrates (organic halides) with Ni(CO)4 as catalyst and CO-source. Nickel carbonyl is extremely toxic and is a very inefficient catalyst. In fact, 600% metal carbonyl catalyst is required for the reaction to proceed. The reactions were base catalysed and relied on the tendency of metal carbonyls to form more electropositive anionic species under basic conditions. These conditions are appropriate exclusively for only a small number of activated systems. Moreover, the use of an external pressure of carbon monoxide gas, even at high pressures, does not improve the efficiency of the catalyst since the external carbon monoxide retards the formation of free sites on the metal Ni.
A recent methodology for carbonylation reactions, hydrocarbonylation reactions or carbonylation cross-coupling reactions (Johansson et al, Organometallics, 1995, 14, 3897) relied on pre-forming a complex between the CO-source and the substrate. This method is limited in that it requires the pre-formation of the metal carbonyl complex with a substrate as well as the pre-activation of said substrate.
It is known that DMF decomposes into carbon monoxide and dimethylamine when heated, cf. e.g. Perrin, D. D., Aremarego, W. L. F. and Perrin, D. R., “Purification of Laboratory Chemicals”, 3rd, Pergamon Press, 1988, pp. 157-158. DMF has also been used for dimethylamination of acid chlorides, cf. Lee, W. S., Park, K. H. and Yoon, Y.-J., “Synthetic Communications” 30(23), pp. 4241-4245 (2000).
In a recent article (Schnyder, A., Beller, M., Mehltretter, G., Nsenda, T., Studer, M. and Indolese, A. F., J. Org. Chem. 2001, 66, 4311-4315 an aminocarbonyl reaction for preparation of primary amides is described. In said aminocarbonylation reaction carbon monoxide gas is used as the CO source and reactions with formamide and dimethyl formamide in the presence of imidazole as the base are described. The highest yields were obtained at temperatures between 90 and 120° C. while at higher temperature (150° C.) nonidentified side products were formed. It is also underlined that CO is a pre-requisite for the formation of aroyl species and that the reaction does not proceed without a CO atmosphere. Different bases were also tested and the fastest reactions were obtained with 4-(dimethylamino) pyridine (DMAP) and 4-pyrrolidinopyridine. A high yield was also obtained with imidazole.